Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function.
Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function.
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DOI：
10.1007/s10162-022-00875-x
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发表时间：
2022-12
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合成糖皮质激素地塞米松通常用于治疗内耳疾病。先前在斑马鱼幼鱼中的研究表明，地塞米松治疗可增强毛细胞再生，但地塞米松也可抑制损伤后周围神经的再生。因此，我们使用斑马鱼模型来确定地塞米松治疗对侧线毛细胞和初级传入的影响。为了探索地塞米松在再生方面的作用，我们使用硫酸铜（CuSO4）诱导毛细胞损失和神经末梢回缩，然后让动物在地塞米松中恢复48 h。与以前的工作相一致，我们观察到地塞米松处理的幼虫中再生的毛细胞显著增加。重要的是，我们发现神经乳头下方的传入过程也在地塞米松的存在下再生并形成适当数量的突触，这表明毛细胞的神经支配不受地塞米松的抑制。除了再生，我们还探讨了长期地塞米松暴露对侧线稳态和功能的影响。地塞米松处理后，我们观察到神经肥大毛细胞和支持细胞的超极化线粒体膜电位（Δ Δ m）。暴露于地塞米松的毛细胞也更容易受到新霉素诱导的细胞死亡。响应于流体喷射递送饱和刺激，通过毛细胞机械转导通道的钙内流显著减少，但突触前钙内流不变。累积起来，这些观察结果表明地塞米松增强了侧线神经瘤中的毛细胞再生，但也破坏了线粒体的稳态，使毛细胞更容易受到耳毒性损伤，并可能影响毛细胞功能。
The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48 h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that the afferent processes beneath neuromasts also regenerated in the presence of dexamethasone and formed an appropriate number of synapses, indicating that innervation of hair cells was not inhibited by dexamethasone. In addition to regeneration, we also explored the effects of prolonged dexamethasone exposure on lateral-line homeostasis and function. Following dexamethasone treatment, we observed hyperpolarized mitochondrial membrane potentials (ΔΨm) in neuromast hair cells and supporting cells. Hair cells exposed to dexamethasone were also more vulnerable to neomycin-induced cell death. In response to a fluid-jet delivered saturating stimulus, calcium influx through hair cell mechanotransduction channels was significantly reduced, yet presynaptic calcium influx was unchanged. Cumulatively, these observations indicate that dexamethasone enhances hair cell regeneration in lateral-line neuromasts, yet also disrupts mitochondrial homeostasis, making hair cells more vulnerable to ototoxic insults and possibly impacting hair cell function.
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影响因子：
3.7
作者：
Ge H;Ni S;Wang X;Xu N;Liu Y;Wang X;Wang L;Song D;Song Y;Bai C
通讯作者：
Bai C
DOI：
10.1523/jneurosci.4559-12.2013
发表时间：
2013-04-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Esterberg R;Hailey DW;Coffin AB;Raible DW;Rubel EW
通讯作者：
Rubel EW
影响因子：
4.9
作者：
Liu, Jing;Peng, Yunhua;Liu, Jiankang
通讯作者：
Liu, Jiankang
DOI：
10.1523/jneurosci.3905-11.2012
发表时间：
2012-03-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Namdaran P;Reinhart KE;Owens KN;Raible DW;Rubel EW
通讯作者：
Rubel EW
影响因子：
1.6
作者：
Gallo, Doris Egli;Khojasteh, Elham;Hegemann, Stefan C. A.
通讯作者：
Hegemann, Stefan C. A.